Skin external composition comprising a sea salt and sugar as active ingredients for preventing and treating vaginosis and the use thereof

ABSTRACT

A skin external composition comprising a combination of salt and sugar as an active ingredient in an amount effective to treat and prevent vaginosis, together with a pharmaceutically acceptable carrier, and the use thereof.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of U.S. National Phase patentapplication Ser. No. 13/501,910, filed on Apr. 13, 2012, which claimspriority to PCT Patent Application No. PCT/KR2010/007068, filed on Oct.15, 2010, Korean Patent Application No. 10-2010-0097774, filed on Oct.7, 2010 and Korean Patent Application No. 10-2009-0099333, filed on Oct.19, 2009; the contents of which are all herein incorporated by thisreference in their entireties. Additionally, this application is aContinuation-in-Part of U.S. Non-Provisional patent application Ser. No.14/025,698, filed on Sep. 12, 2013, which is a Divisional of U.S.National Phase patent application Ser. No. 13/501,910, filed on Apr. 13,2012, which claims priority to PCT Patent Application No.PCT/KR2010/007068, filed on Oct. 15, 2010, Korean Patent Application No.10-2010-0097774, filed on Oct. 7, 2010 and Korean Patent Application No.10-2009-0099333, filed on Oct. 19, 2009; the contents of which are allherein incorporated by this reference in their entireties. Additionally,this application is a Continuation-in-Part of U.S. Non-Provisionalpatent application Ser. No. 14/025,654, filed on Sep. 12, 2013, which isa Continuation-in-Part of U.S. National Phase patent application Ser.No. 13/501,910, filed on Apr. 13, 2012, which claims priority to PCTPatent Application No. PCT/KR2010/007068, filed on Oct. 15, 2010, KoreanPatent Application No. 10-2010-0097774, filed on Oct. 7, 2010 and KoreanPatent Application No. 10-2009-0099333, filed on Oct. 19, 2009; thecontents of which are all herein incorporated by this reference in theirentireties. All publications, patents, patent applications, databasesand other references cited in this application, all related applicationsreferenced herein, and all references cited therein, are incorporated byreference in their entirety as if restated here in full and as if eachindividual publication, patent, patent application, database or otherreference were specifically and individually indicated to beincorporated by reference.

BACKGROUND OF THE INVENTION

The present application relates to an external skin compositioncomprising a salt and a sugar as active ingredients for preventing andtreating vaginosis and the use thereof.

Vaginitis is a condition that occurs especially during pregnancy in thevagina causing vaginal discharge, inflammation, and irritation, as wellas, vulvar or vaginal itching. The three most common vaginal infectionsand diseases are also the most frequent causes of vaginitis. The threecommon vaginal infections include: bacterial vaginosis, vaginal yeastinfection, and trichomoniasis.

The human vagina is colonized with various microbes, yeasts and germs,for example, about more than 10⁴ numbers/ml (vaginal fluid) ofLactobacillus spp. such as, Lactobacillus crispatus and Lactobacillusjensenii, which provide a weak acidic environment ranging from pH4.5-5.1 to protect from a microbial infection. Additionally, the vaginais a highly versatile organ that can profoundly affect the health ofwomen and their newborn infants. It has been reported that there aremany important pathogens in the vaginal niche, such as, Neiserriagonorrhea, Ureaplasma species, Mycoplasma genitalium, Streptococcusspecies, Escherichia coli, Chlamydia trachomatis, and Trichomonasvaginalis, etc.

Bacterial vaginosis (BV), the most prevalent and detrimental vaginosis,gives rise to malodorous vaginal discharge or local irritation of thewoman with BV and is associated with several more serious adverseoutcomes including preterm birth, pelvic inflammatory disease, andacquisition of HIV infection. Women with bacterial vaginosis (BV) havelost many Lactobacillus species (except L. iners) and have acquired avariety of anaerobic and facultative bacteria. Gram stains of vaginalfluid from women with BV show a loss of Gram-positive rods and theirreplacement with Gram-negative and Gram-variable cocci and rods.Cultures of vaginal fluid from subjects with BV typically yieldGardnerella vaginalis and a mixture of other bacteria that may includePeptosterptococcus, Mobiluncus, Bacterioides, Prevotella, Porphyromonas,Mobiluncus and Mycoplasma species. (Sujatha Srinivasan and David N.Fedricks, Review Article, The Human Vaginal Bacterial Biota andBacterial Vaginosis, Interdisciplinary Perspectives on InfectiousDiseases, Vol., 2008, Article ID 750479, pp 1-3).

There have been studies to develop effective therapies to treatvaginitis, for example, orally administrated broad spectrum antibiotics,such as, metronidazole. However, this therapy has many disadvantages,such as, antibiotic intolerance, systemic toxicity in case of long-termadministration, and a probable destruction of the normal bacterial florain the vagina. These treatments cause secondary complications, such as,a decreased number of Lactobacillus spp., an increase of vaginal pH, anda proliferation of anaerobic microbes.

Accordingly, there is a need to develop novel therapeutic compositionsshowing treatments with long-term activity and safety to treatvaginosis.

However, there has never been a treatment reported or disclosed on theuse of a composition with a combination of salt and sugar with atherapeutic effect on vaginosis. None of the above cited references,which are incorporated herein by reference, disclose a treatment using acombination of salt and sugar.

The applicants have carried out antibacterial test, especiallyGardnerella vaginalis, a main cause of vaginosis, to investigate theinhibitory effect of a combination of salt and sugar on vaginosis. Theresults of these tests confirmed that a combination of salt and sugarshowed potent antibacterial activity.

These results and other disclosures will become apparent from thedetailed disclosure of the discoveries provided hereinafter.

BRIEF SUMMARY OF INVENTION

Accordingly, an embodiment of the present disclosure is an external skincomposition comprising a combination of salt and sugar as an activeingredient in an amount effective to treat or prevent vaginosis,together with a pharmaceutically acceptable carrier.

Another embodiment of the present disclosure is a use of a combinationof salt and sugar in the manufacture of a medicament employed fortreating or preventing vaginosis in a mammal.

Another embodiment of the present disclosure is a method of treating orpreventing vaginosis in a mammal wherein the method comprisesadministering to said mammal an effective amount of a combination ofsalt and sugar, together with a pharmaceutically acceptable carrierthereof.

DETAILED DESCRIPTION OF THE INVENTION

One embodiment of the present disclosure is an external skin compositioncomprising a combination of salt and sugar as an active ingredient in anamount effective to treat or prevent vaginosis, together with apharmaceutically acceptable carrier.

Another embodiment of the present disclosure is a use of a combinationof salt and sugar in the manufacture of a medicament employed fortreating or preventing vaginosis in a mammal.

Another embodiment of the present disclosure is a method of treating orpreventing vaginosis in a mammal wherein the method comprisesadministering to said mammal an effective amount of a combination ofsalt and sugar together with a pharmaceutically acceptable carrierthereof.

The term, “salt” defined herein comprises natural salts (unrefined saltfrom sea or brine ponds and mined mineral salt) or processed salts(refined salts to eliminate trace compounds and/or to add compounds(e.g., fluoride). Sea salts from Korea and other coastal countries areespecially good for the disclosed purpose of treating vaginosis in amammal. Also, included in the definition of “salt” are a pure salt,sodium chloride, melted salt [also called molten salt], or melted[molten] natural salt. Melted [molten] salt is a salt which is solid atstandard temperature and pressure (STP) but enters the liquid phase whenheated. Melted [molten] salt is prepared by melting the salt at atemperature ranging from 200 to 2000° C., or commonly from 800 to 1200°C., for a period ranging from 2 hours to 7 days or commonly 12 hours to48 hours.

Sea salt is salt produced from the evaporation of seawater. The colorsand variety of flavors are due to local clays and algae found in thewaters the salt is harvested from. For example, some boutique salts fromKorea and France are pinkish gray, some from India are black.

The chemical composition of sea salt is typically the same as the ionsdissolved in seawater. By dry weight percent: Sodium, 30.8; Potassium,1.1; Magnesium, 3.7; Calcium, 1.2; Chloride, 55.5; Sulfate, 7.7.However, a study found the amount of trace elements, such as titanium,silver, cobalt, and lead in synthetic sea salt are much higher thanthose in sea water. The magnitude of the difference can be as large as10⁴ times.

Unrefined sea salt contains small amounts of magnesium and calciumhalides and sulphates, traces of algal products, salt-resistant bacteriaand sediment particles. The calcium and magnesium salts confer a faintlybitter overtone, and they make unrefined sea salt hygroscopic (i.e., itgradually absorbs moisture from air if stored uncovered). Algal productscontribute a mild “sea-air” smell, the latter from organobrominecompounds. Sediments, the proportion of which varies with the source,give the salt a dull grey appearance.

The mineral content also affects the taste. Taste and aroma compoundsare often detectable by humans in minute concentrations; sea salt mayhave a more complex flavor than pure sodium chloride.

Different natural salts have different mineralities depending on theirsource, giving each one a unique flavor. Fleur de sel, a natural seasalt from the surface of evaporating brine in salt pans, has a uniqueflavor varying with the region from which it is produced.

In traditional Korean cuisine, so-called “bamboo salt” is prepared byroasting salt at temperatures between 800 and 2000° C. in a bamboocontainer plugged with mud at both ends. This product absorbs mineralsfrom the bamboo and the mud.

Melted Salt originates from Korea. It was originally developed by Koreandoctors and monks almost 1,000 years ago as a folk medicinal remedy forvarious illnesses. The Melted Salt was originally made by putting seasalt into cases made from bamboo trunks.

After the salt was inserted into the trunks, the ends were sealed withnatural yellow clay that was rich in minerals. The trunks were thenroasted in a furnace. The process required 10 hours of roasting at atemperature between 1,000° to 1,500° C. This procedure could be repeatedfrom three to nine times.

Through repeated experimentations, doctors discovered that Melted Saltgained higher medical effectiveness if it was baked for more time. Thismethod enhanced the amalgamation of minerals from the yellow clay intothe sea salt.

Additionally, the numerous high-heat roasting process was more effectivein ridding of impurities in the sea salt.

It has been found that the salt reaches its highest medical efficacywhen it is baked for 9 times. Melted Salt is labeled as 1×, 3×, 6×, 9×indicating the number of roasting processes the specific Melted Salt hasreceived. Because the medical efficacy correlates with the amount ofroasting procedures, the price range can differ significantly dependingon the number of roasting processes.

Melted Salt contains many minerals due to the leaching of minerals. Themain components of Melted Salt are calcium, phosphorus, magnesium, iron,manganese, copper, potassium, and zinc. Melted Salt is highly alkalinein contrast to other salts which are acidic. This also makes Melted Salta great neutralizer.

Sea salt tends to be coarser than table salt. Unrefined sea salt isfound to have many minerals that regular table salt lacks such aspotassium, magnesium, calcium, and iodine. Because of this, a lot ofpeople use sea salts instead of table salts.

Salts, in general, can suppress fungal and bacterial growth. Melted Saltexcels in comparison to other salts. As a matter of fact, it has beenshown in clinical studies that Melted Salt can actually preventSalmonella infection.

Melted Salt, unlike other salts that are acidic, is highly alkaline (pHof 10.5) because of the high sulfur content. Therefore, it can act as aneutralizer for acidic food. Also because of this unique property, theiron in Melted Salt does not oxidize like the iron in other salts.Melted Salt produces reduction reactions. It suppresses inflammationsand slows down cell proliferation.

The most salt is made by evaporating water from a brine and ispositively charged. However, since Melted Salt is made by melting saltat a high temperature and then cooling to a solid, it is negativelycharged.

The term, “sugar” defined herein comprises a saccharide compound:mono-saccharides, such as, glucose, fructose, mannose, galactose, etc.and disaccharides, such as, lactose, maltose, sugar, etc. Glucose orcrystalline glucose show good results when used in compositions to treatvaginosis.

The term, “a combination of salt and sugar” defined herein comprise acombination of salt and sugar mixed at a ration in a composition. Oneembodiment of the ratio is a salt:sugar ratio of 1:1-30 (w/w). Anotherembodiment of the ratio is a salt:sugar ratio of 1:1-10 (w/w). Anotherembodiment of the ratio is a salt:sugar ratio of 1:1-5 (w/w). Anotherembodiment of the ratio is a salt:sugar ratio of 1:1-3 (w/w). Therefore,the amount of sugar is equal to or up to 30 times greater than theamount of salt.

The term, “vaginosis” defined herein comprises a vaginosis selected frombacterial vaginosis, especially Gardnerella vaginalis; fungal vaginitisand Tricomonas vaginitis.

The composition of the present disclosure may further contain otheringredients, i.e., antibiotics, dyes, and flavors, in an amount fromabout 0.1 to about 20% by weight of the above composition based on thetotal weight of the composition. If the composition contains otheringredients, the quantity of sugar and salt is in an amount from about99.9% to about 80% by weight.

Hereinafter, the present disclosure is described in detail.

A composition of the disclosure comprising the combination of salt andsugar can be prepared in detail by following procedures,

For example, a cleansing combination of the present disclosure can beprepared as follows: a natural salt or processed salt is melted at atemperature ranging from 200 to 2000° C. for the period ranging from 2hours to 7 days to obtain the melted salt of the first step. The meltedsalt is mixed with a sugar compound with a salt:sugar ratio of 1:1-30(w/w) to obtain the disclosed combination. Then the combination isdissolved in an appropriate amount of distilled water, buffer, orisotonic solution with an appropriate amount of other additives (ifneeded), such as, the antibiotics, dyes, or flavors to obtain thecleansing composition.

It have been proven that the composition comprising a combination ofsalt and sugar prepared by the above-described method showed potentantibacterial activity, especially against Gardnerella vaginalis, a maincause of vaginosis, as well as, stimulating the production of lacticacid to maintain the vagina acidity by way of stimulating theproliferation of Lactobacillus acidophilus.

Accordingly, external skin composition is disclosed comprising acombination of salt and sugar prepared by the above-described method fortreating or preventing vaginosis, together with a pharmaceuticallyacceptable carrier.

Additionally, the present application discloses a use of a combinationof salt and sugar prepared by the above-described method in themanufacture of a medicament employed for treating or preventingvaginosis disease in a mammal.

Additionally, the present application discloses a method of treating orpreventing vaginosis disease in a mammal wherein the method comprisesadministering to said mammal an effective amount of a combination ofsalt and sugar prepared by the above-described method, together with apharmaceutically acceptable carrier thereof.

The term “prevent” defined herein means the inhibition of diseases in amammal which is prone to catch these diseases and the term “treat” usedherein means (a) the inhibition of the development of disease orillness; (b) the alleviation of disease or illness; or (c) theelimination of disease or illness.

The disclosed composition may additionally comprise conventionalcarrier, adjuvants or diluents in accordance with using the method. Itis suggested that the carrier used be an appropriate substance accordingto the usage and application method, but it is not limited. Appropriatediluents are listed in the written text of Remington's PharmaceuticalScience (Mack Publishing Co, Easton Pa.).

Hereinafter, the following formulation methods and excipients are merelyexemplary and in no way limit the disclosure.

The composition according to the present disclosure can be provided asan external skin composition containing pharmaceutically acceptablecarriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose,sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acaciarubber, alginate, gelatin, calcium phosphate, calcium silicate,cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxy benzoate, talc, magnesium stearate and mineraloil. The formulations may additionally include fillers,anti-agglutinating agents, lubricating agents, wetting agents, flavoringagents, emulsifiers, preservatives and the like. The compositions of thepresent disclosure may be formulated so as to provide quick, sustainedor delayed release of the active ingredient after their administrationto a patient by employing any of the procedures well known in the art.

For example, the compositions of the present disclosure can be dissolvedin distilled water, pH buffer, oils, propylene glycol or other solventsthat are commonly used in the art. Suitable examples of the carriersinclude physiological saline, polyethylene glycol, ethanol, vegetableoils, isopropyl myristate, etc., but are not limited to them. Fortopical administration, the compounds of the present disclosure can beformulated in the form of ointments and creams.

The external skin composition of the present disclosure may be preparedin any form, for example, topical preparation such as cleansing liquid,gel, jelly, foam, cream, ointment, lotion, balm, patch, paste, spraysolution, aerosol and the like, or insert preparation such as vaginaltablet, vaginal capsule, vaginal film, vaginal sponge, tampon, pad etc,preferably, vaginal tablet composition or cleansing liquid composition.

Accordingly, the present disclosure provides a cleansing liquid solutionor vaginal tablet composition comprising a combination of salt and sugarfor treating or preventing vaginosis, together with a pharmaceuticallyacceptable carrier.

The composition of the present disclosure in pharmaceutical dosage formsmay be used in the form of their pharmaceutically acceptable salts, andalso may be used alone or in appropriate association, as well as, incombination with other pharmaceutically active compounds, such as,antibacterial compounds or extracts derived from plants, animals orminerals well-known in the art.

The desirable dose of the present disclosure varies depending on thecondition and the weight of the subject, severity, drug form, route andperiod of administration, and may be chosen by those skilled in the art.However, in order to obtain desirable effects, it is generallyrecommended to administer at the amount ranging from 0.001 mg/kg to 1000mg/kg or an amount ranging from 0.01 mg/kg to 100 mg/kg by weight of thepatient per day of the combination of the present disclosure. The dosemay be administered in single or divided into several times per day.

In terms of composition, in one embodiment, the disclosed combination isbetween 0.01% to 99.99% by weight based on the total weight of thecomposition. In another embodiment, the disclosed combination is between0.1% to 99% by weight based on the total weight of the composition. Inanother embodiment, the disclosed combination is between 1% to 20% byweight based on the total weight of the composition. In anotherembodiment, the disclosed combination is between 5% to 10% by weightbased on the total weight of the composition.

The composition of the present disclosure can be administered to asubject animal, such as, mammals (rat, mouse, domestic animals or human)via various routes. All modes of administration are contemplated; forexample, administration can be made externally, topically, orally,rectally or by intravenous, intramuscular, subcutaneous, intracutaneous,intrathecal, epidural or intracerebroventricular injection.

Additional embodiments are described in the following paragraphs.

Paragraph 1. A composition comprising: a melted salt and a sugar;wherein the melted salt and sugar have a mixed weight ratio from 1:1 to1:30, wherein the weight of the sugar is equal to or greater than theweight of any other ingredient in the composition and wherein the totalweight of the sugar and the melted salt is from 80% to 100% of the totalweight of the composition.

Paragraph 2. The composition of Paragraph 1 wherein the melted salt is amelted sea salt.

Paragraph 3. The composition of Paragraph 1 wherein the melted sea saltis melted sodium chloride.

Paragraph 4. The composition of Paragraph 1, wherein the sugar isglucose.

Paragraph 5. The composition of Paragraph 1 wherein composition is atopical preparation selected from the group consisting of a cleansingliquid, gel, jelly, foam, cream, ointment, lotion, balm, patch, paste,spray solution, and aerosol.

Paragraph 6. The composition of Paragraph 5 wherein the composition is acleansing liquid.

Paragraph 7. The composition of Paragraph 1 wherein composition is aninsert preparation selected from the group consisting of tablet,capsule, film, sponge, tampon and pad.

Paragraph 8. The composition of Paragraph 7 wherein the composition is atablet.

Paragraph 9. The composition of Paragraph 1, further comprisingdissolving the composition in a liquid at a percentage of thecomposition to the liquid from 0.01% to 99.99%.

Paragraph 10. The composition of Paragraph 9, wherein the percentage ofthe composition to the liquid is from 5% to 10%.

Paragraph 11. The composition of Paragraph 9, wherein the liquid isselected from the group consisting of distilled water, a bufferedsolution, an isotonic solution, a physiological saline, an oil,propylene glycol, ethanol and isopropyl myristate.

Paragraph 12. A method of treatment comprising a) administering to amammal the composition of Paragraph 1; and b) placing the composition ina vagina of the mammal in need of treatment for a bacterial vaginosisinfection, wherein the bacterial vaginosis infection is a Gardnerellavaginalis infection.

Paragraph 13. The method of Paragraph 12, wherein the treatment isselected from the group consisting of inhibition of development of theGardnerella vaginalis infection, alleviation of the Gardnerellavaginalis infection and elimination of the Gardnerella vaginalisinfection.

Paragraph 14. The method of Paragraph 12, wherein administering to themammal comprises administering an amount of the composition in Paragraph1 ranging from 0.001 mg to 1000 mg per kilogram of body weight of themammal.

Paragraph 15. The method of Paragraph 14, wherein the amount of thecomposition in Paragraph 1 ranges from 0.01 mg to 100 mg per kilogram ofbody weight of the mammal.

Paragraph 16. The method of Paragraph 12, wherein the composition isadministered from once a day to several times per day.

Paragraph 17. A composition comprising: a sea salt and a sugar; whereinthe sea salt and sugar have a mixed weight ratio from 1:1 to 1:30,wherein the weight of the sugar is equal to or greater than the weightof any other ingredient in the composition and wherein the total weightof the sugar and the sea salt is from 80% to 100% of the total weight ofthe composition.

Paragraph 18. The composition of Paragraph 17 wherein the sea salt issodium chloride.

Paragraph 19. The composition of Paragraph 17, wherein the sugar isglucose.

Paragraph 20. The composition of Paragraph 17 wherein composition is atopical preparation selected from the group consisting of a cleansingliquid, gel, jelly, foam, cream, ointment, lotion, balm, patch, paste,spray solution, and aerosol.

Paragraph 21. The composition of Paragraph 20 wherein the composition isa cleansing liquid.

Paragraph 22. The composition of Paragraph 17 wherein composition is aninsert preparation selected from the group consisting of tablet,capsule, film, sponge, tampon and pad.

Paragraph 23. The composition of Paragraph 22 wherein the composition isa tablet.

Paragraph 24. The composition of Paragraph 17, further comprisingdissolving the composition in a liquid at a percentage of thecomposition to the liquid from 0.01% to 99.99%.

Paragraph 25. The composition of Paragraph 24, wherein the percentage ofthe composition to the liquid is from 5% to 10%.

Paragraph 26. The composition of Paragraph 24, wherein the liquid isselected from the group consisting of distilled water, a bufferedsolution, an isotonic solution, a physiological saline, an oil,propylene glycol, ethanol and isopropyl myristate.

Paragraph 27. A method of treatment comprising a) administering to amammal the composition of Paragraph 17; and b) placing the compositionin a vagina of the mammal in need of treatment for a bacterial vaginosisinfection, wherein the bacterial vaginosis infection is a Gardnerellavaginalis infection.

Paragraph 28. The method of Paragraph 27, wherein the treatment isselected from the group consisting of inhibition of development of theGardnerella vaginalis infection, alleviation of the Gardnerellavaginalis infection and elimination of the Gardnerella vaginalisinfection.

Paragraph 29. The method of Paragraph 27, wherein administering to themammal comprises administering an amount of the composition in Paragraph1 ranging from 0.001 mg to 1000 mg per kilogram of body weight of themammal.

Paragraph 30. The method of Paragraph 29, wherein the amount of thecomposition in Paragraph 1 ranges from 0.01 mg to 100 mg per kilogram ofbody weight of the mammal.

Paragraph 31. The method of Paragraph 27, wherein the composition isadministered from once a day to several times per day.

Paragraph 32. A composition comprising: a combination of sodium chlorideand glucose at a mixed weight ratio from 1:1 to 1:30, wherein the weightof the glucose is equal to or greater than the weight of any otheringredient in the composition and wherein the total weight of theglucose and the sodium chloride is from 80% to 100% of the total weightof the composition.

Paragraph 33. The composition of Paragraph 32 wherein composition is atopical preparation selected from the group consisting of a cleansingliquid, gel, jelly, foam, cream, ointment, lotion, balm, patch, paste,spray solution, and aerosol.

Paragraph 34. The composition of Paragraph 33 wherein the composition isa cleansing liquid.

Paragraph 35. The composition of Paragraph 32 wherein composition is aninsert preparation selected from the group consisting of tablet,capsule, film, sponge, tampon and pad.

Paragraph 36. The composition of Paragraph 35 wherein the composition isa tablet.

Paragraph 37. The composition of Paragraph 32, further comprisingdissolving the composition in a liquid at a percentage of thecomposition to the liquid from 0.01% to 99.99%.

Paragraph 38. The composition of Paragraph 37, wherein the percentage ofthe composition to the liquid is from 5% to 10%.

Paragraph 39. The composition of Paragraph 37, wherein the liquid isselected from the group consisting of distilled water, a bufferedsolution, an isotonic solution, a physiological saline, an oil,propylene glycol, ethanol and isopropyl myristate.

Paragraph 40. A method of treatment comprising a) administering to amammal the composition of Paragraph 32; and b) placing the compositionin a vagina of the mammal in need of treatment for a bacterial vaginosisinfection, wherein the bacterial vaginosis infection is a Gardnerellavaginalis infection.

Paragraph 41. The method of Paragraph 40, wherein the treatment isselected from the group consisting of inhibition of development of theGardnerella vaginalis infection, alleviation of the Gardnerellavaginalis infection and elimination of the Gardnerella vaginalisinfection.

Paragraph 42. The method of Paragraph 40, wherein administering to themammal comprises administering an amount of the composition in Paragraph1 ranging from 0.001 mg to 1000 mg per kilogram of body weight of themammal.

Paragraph 43. The method of Paragraph 42, wherein the amount of thecomposition in Paragraph 1 ranges from 0.01 mg to 100 mg per kilogram ofbody weight of the mammal.

Paragraph 44. The method of Paragraph 40, wherein the composition isadministered from once a day to several times per day.

Paragraph 45. A composition comprising: a melted salt and a sugar;wherein the melted salt and sugar have a mixed weight ratio from 1:1 to1:30, wherein the weight of the sugar is equal to or greater than theweight of any other ingredient in the composition and wherein the totalweight of the sugar and the melted salt is from 30% to 100% of the totalweight of the composition.

Paragraph 46. The composition of Paragraph 45, wherein the total weightof the sugar and the melted salt is from 50% to 100% of the total weightof the composition

Paragraph 47. The composition of Paragraph 45, wherein the melted saltis a melted sea salt.

Paragraph 48. The composition of Paragraph 45, wherein the melted seasalt is melted sodium chloride.

Paragraph 49. The composition of Paragraph 45, wherein the sugar isglucose.

Paragraph 50. The composition of Paragraph 45, wherein composition is atopical preparation selected from the group consisting of a cleansingliquid, gel, jelly, foam, cream, ointment, lotion, balm, patch, paste,spray solution, and aerosol.

Paragraph 51. The composition of Paragraph 50, wherein the compositionis a cleansing liquid.

Paragraph 52. The composition of Paragraph 45, wherein composition is aninsert preparation selected from the group consisting of tablet,capsule, film, sponge, tampon and pad.

Paragraph 53. The composition of Paragraph 52, wherein the compositionis a tablet.

Paragraph 54. The composition of Paragraph 45, further comprisingdissolving the composition in a liquid at a percentage of thecomposition to the liquid from 0.01% to 99.99%.

Paragraph 55. The composition of Paragraph 54, wherein the percentage ofthe composition to the liquid is from 5% to 10%.

Paragraph 56. The composition of Paragraph 54, wherein the liquid isselected from the group consisting of distilled water, a bufferedsolution, an isotonic solution, a physiological saline, an oil,propylene glycol, ethanol and isopropyl myristate.

Paragraph 57. A method of treatment comprising a) administering to amammal the composition of Paragraph 45; and b) placing the compositionin a vagina of the mammal in need of treatment for a bacterial vaginosisinfection, wherein the bacterial vaginosis infection is a Gardnerellavaginalis infection.

Paragraph 58. The method of Paragraph 57, wherein the treatment isselected from the group consisting of inhibition of development of theGardnerella vaginalis infection, alleviation of the Gardnerellavaginalis infection and elimination of the Gardnerella vaginalisinfection.

Paragraph 59. The method of Paragraph 57, wherein administering to themammal comprises administering an amount of the composition in Paragraph45 ranging from 0.001 mg to 1000 mg per kilogram of body weight of themammal.

Paragraph 60. The method of Paragraph 59, wherein the amount of thecomposition in Paragraph 1 ranges from 0.01 mg to 100 mg per kilogram ofbody weight of the mammal.

Paragraph 61. The method of Paragraph 57, wherein the composition isadministered from once a day to several times per day.

Paragraph 62. A composition comprising: a sea salt and a sugar; whereinthe sea salt and sugar have a mixed weight ratio from 1:1 to 1:30,wherein the weight of the sugar is equal to or greater than the weightof any other ingredient in the composition and wherein the total weightof the sugar and the sea salt is from 30% to 100% of the total weight ofthe composition.

Paragraph 63. The composition of Paragraph 62, wherein the sea salt issodium chloride.

Paragraph 64. The composition of Paragraph 62, wherein the sugar isglucose.

Paragraph 65. The composition of Paragraph 62, wherein the compositionis an insert preparation.

Paragraph 66. The composition of Paragraph 65, wherein the insertpreparation is selected from the group consisting of a tablet, acapsule, a film, a sponge, a tampon, and a pad.

Paragraph 67. The composition of Paragraph 62, wherein the compositionis a topical preparation.

Paragraph 68. The composition of Paragraph 67, wherein the topicalpreparation is selected from the group consisting of a cleansing liquid,a gel, a jelly, a foam, a cream, an ointment, a lotion, a balm, a patch,a paste, a spray solution and an aerosol.

Paragraph 69. The composition of Paragraph 62, further comprisingdissolving the composition in a liquid at a percentage of thecomposition to the liquid from 0.01% to 99.99%.

Paragraph 70. The composition of Paragraph 69, wherein the percentage ofthe composition to the liquid is from 5% to 10%.

Paragraph 72. The composition of Paragraph 69, wherein the liquid isselected from the group consisting of distilled water, a bufferedsolution, an isotonic solution, a physiological saline, an oil,propylene glycol, ethanol and isopropyl myristate.

Paragraph 73. A method of treatment comprising a) administering to amammal the composition of Paragraph 62; and b) placing the compositionin a vagina of the mammal in need of treatment for a bacterial vaginosisinfection, wherein the bacterial vaginosis infection is a Gardnerellavaginalis infection.

Paragraph 74. The method of Paragraph 73, wherein the treatment isselected from the group consisting of inhibition of development of theGardnerella vaginalis infection, alleviation of the Gardnerellavaginalis infection and elimination of the Gardnerella vaginalisinfection.

Paragraph 75. The method of Paragraph 73, wherein administering to themammal comprises administering an amount of the composition in Paragraph1 ranging from 0.001 mg to 1000 mg per kilogram of body weight of themammal.

Paragraph 76. The method of Paragraph 75, wherein the amount of thecomposition in Paragraph 1 ranges from 0.01 mg to 100 mg per kilogram ofbody weight of the mammal.

Paragraph 77. The method of Paragraph 73, wherein the composition isadministered from once a day to several times per day.

Paragraph 78. A composition consisting essentially of a combination ofsodium chloride, glucose and a pharmaceutically acceptable carrier.

Paragraph 79. The method of Paragraph 78, wherein the composition isselected from the group consisting of a topical preparation and aninsert preparation.

Paragraph 80. The method of Paragraph 79, wherein the topicalpreparation is selected from the group consisting of a cleansing liquid,a gel, a jelly, a foam, a cream, an ointment, a lotion, a balm, a patch,a paste, a spray solution and an aerosol.

Paragraph 81. The composition of Paragraph 80 wherein the composition isa cleansing liquid.

Paragraph 82. The method of Paragraph 79, wherein the insert preparationis selected from the group consisting of a tablet, a capsule, a film, asponge, a tampon, and a pad.

Paragraph 83. The composition of Paragraph 82 wherein the composition isa tablet.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the compositions, use andpreparations of the present disclosure without departing from the spiritor scope of the disclosure.

EXAMPLES

The following Examples and Experimental Examples are intended to furtherillustrate the present disclosure without limiting its scope.

Example 1 Preparation of the Combinations Preparation of Melted Salt

900 mg of natural sea salt (Shinan, Korea) was melted for 24 hours at850°-1000° C. using a heater (MS-E104, TOPS Co. Ltd.) to obtain 400 mgof the melted salt.

Preparation of Pure Salt

400 mg of pure salt (NaCl, F.W. 58.44) was procured from Duksan Co.,Korea (SPPO-91701).

Preparation of Glucose

800 mg of glucose (crystalline glucose) was procured from Samyang GenexCorp., Korea.

Preparation of Combination (1)

400 mg of the melted salt and 800 mg of glucose prepared in the abovesteps, were thoroughly mixed together to obtain 1200 mg of thecombination (designated as “SG1” hereinafter).

Preparation of Combination (2)

400 mg of the pure salt (sodium chloride) and 800 mg of glucose preparedin the above steps, were thoroughly mixed together to obtain 1200 mg ofthe combination (designated as “SG4” hereinafter).

The combinations were kept at −75° C. in a refrigerator and used in thefollowing experiments by dissolving in distilled water before use.

Example 2 Preparation of Vaginal Tablet Composition

The combination prepared in Example 1 comprising 400 mg of melted saltand 800 mg of glucose was mixed with 2 mg of magnesium stearate in orderto formulate the vaginal tablet composition combination (designated as“SG2” hereinafter) using an entableting apparatus (KT2000,Kumsungkigong).

Example 3 Preparation of Vaginal Cleansing Solution Composition

The vaginal cleansing solution composition comprising the combinationprepared in Example 1 comprising 400 mg of pure salt and 800 mg ofglucose was prepared by mixing for 48 hours with stirring with thefollowing ingredients as shown in Tablet 1 (designated as “SG3”hereinafter).

TABLE 1 SG3 solution (100 ml) Ingredient Amount SG4 0.5 g Lactic acid 1g adjuvant Whey 180 mg Ethanol 1 g Preservatives (benzalkonimum HCl andTrace Trace amount amount menthol) Distilled water Appropriate amount toadjusted to 100 ml

Reference Example 1 Preparation & Reagent Experimental Strains

For use in the following tests, two strains, (1) Lactobacillusacidophilus strain (KRIBB deposit No. KCTC 1120) and (2) Gadnerellavaginalis strain (KRIBB deposit No. KCTC 5096) were procured from KCTC(Korean Collection for Type Culture in KRIBB (Korea Research Instituteof Bioscience & Biotechnology) and cultured in liquid medium(thioglycollate Medium, DIFCO™) at 37° C. or solid medium (blood agarplate) at 37° C. according to anaerobic pouch method (GasPak™, EZ PouchSystem).

Materials

Combination (SG1) prepared in Example 1 was used as a test sample andlactic acid (Fluka Co., ACS reagent, 85-90%, L-lactic acid in water) wasused in the experiment.

Experimental Example 1 Effect on the Growth of Lactobacillus acidophilus

To test the effect of the combination prepared in Example 1 on thegrowth of Lactobacillus acidophilus, the following test was performedaccording to the procedure disclosed in the literature (Choi, J. G. etal., Antibacterial activity of Ecklonia cava againstmethicillin-resistant Staphylococcus aureus and Salmonella spp.,Foodborne Pathog. Dis., 2010 (April: 7(4), pp 435-441).

Lactobacillus acidophilus strain (KRIBB deposit No. KCTC 1120) wasinoculated into a fresh blood agar plate and cultured in liquid medium(thioglycollate Medium, DIFCO™) at 37° C. at the concentration of 10⁵/mland various concentrations of the test sample, i.e., 0 mg/ml (negativecontrol), 0.001 mg/ml, 0.1 mg/ml and 10 mg/ml of SG1 and SG4 weretreated thereto. The optical density (OD) value was determined using aphotometer (Densimat, 50015-PONTE A EMA (F1); Biomerieux Italia S. P. A)in order to check the growth of the stain at 4, 8, 12 and 24 hours afterthe treatment.

The results can be seen in Table 2. The test sample groups treated withcombination SG1 and SG4 showed an increasing effect on the production oflactic acid, which maintains the pH of the vaginal environment and thegrowth of Lactobacillus acidophilus.

TABLE 2 Effect on the growth of Lactobacillus acidophilus Conc. O.D. ofLactobacillus acidophilus Sample mg/ml 4 hrs. 8 hrs. 12 hrs. 24 hrs.CONTROL 0 0.2 0.6 1.2 3.6 SG1 0.001 0.2 0.6 1.2 3.9 0.1 0.2 0.6 1.4 4.110 0.2 0.7 1.5 4.3 SG4 0.001 0.2 0.7 1.2 4.0 0.1 0.2 0.8 1.5 4.2 10 0.20.8 1.6 4.4

Experimental Example 2 Effect on the Growth of Gadnerella vaginalis

To test the effect of the combination prepared in Example 1 on thegrowth of Gadnerella vaginalis, a main cause of vaginosis, the followingdisk diffusion test was performed according to the procedure disclosedin the literature (Choi, J. G. et al., Antibacterial activity ofHylomecon hylomeconoides against methicillin-resistant Staphylococcusaureus, Appl. Biochem. Biotechnol., 2010 (April: 160(8), pp 2467-2474).

Gadnerella vaginalis strain (KRIBB deposit No. KCTC 5096) was inoculatedinto a fresh blood agar plate and cultured in 6 mm disk treated with 20microliter of various concentrations of lactic acid, i.e., 0 μg/ml(Control), 0.2 μg/ml, 2 μg/ml, and 20 μg/ml of SG1 and SG4 for 24 hours.The inhibition distance (mm) of each disk was determined.

Vaginosis occurs by hyper-proliferation of anaerobic microbes caused bydecreased growth of Lactobacillus spp. Accordingly, the treatment oflactic acid with Gadnerella vaginalis strains forms an effectiveinhibition zone in the disk. It is regarded that the production oflactic acid inhibited the growth of Gadnerella vaginalis strain, a maincause of vaginosis.

The results can be seen in Table 3. The test sample groups treated withthe combinations SG1 and SG4 potently inhibited the growth of Gadnerellavaginalis strain in a dose dependent manner. Therefore, the combinationsof SG1 and SG4 can be useful in treating or preventing vaginosis sincethey showed potent inhibitory effects on the growth of Gadnerellavaginalis.

TABLE 3 Effect on the growth of Gadnerella vaginalis Treatmentconcentration of lactic acid with disk (20 μl/disk) Inhibition diameter(mm) Concentration SG1 SG4 Control 7 8 0.2 μg/ml 10 12   2 μg/ml 18 19 20 μg/ml 25 28

Experimental Example 3 Brief Clinical Test (1)

1200 mg of the vaginal tablet composition (SG2) prepared in Example 2was administrated intra-vaginally once a day for 5 days to 100volunteers consisting of 35 patients suffering from vaginosis, and 65normal women ranging from 20 to 50 years who live in Korea. A directsurvey on the effects of the composition was performed.

The survey result on (A) the inhibition effect on unpleasant scent, (B)feeling of freshness and (C) alleviation effect on skin pruritus wasclassified into 4 categories, i.e., (1) very satisfied (2) satisfied,(3) common and (4) dissatisfied according to the intensity of eachcontent. The results are shown in Table 4.

TABLE 4 Survey result Content Very satisfied Satisfied CommonDissatisfied Sum A 79 15 4 2 100 B 72 14 10 4 100 C 67 18 12 3 100

The results can be seen in Table 4. More than 94% of the people in thetest group treated with combination SG2 were satisfied with (A) theinhibition effect on unpleasant scent, and more than 86% of the peoplein the test group treated with combination SG2 were satisfied with (B)the feeling of freshness. Furthermore, more than 85% of the people inthe test group treated with combination SG2 were satisfied with (C) thealleviation effect on skin. Therefore, the combination SG2 can be usefulin treating or preventing vaginosis.

Experimental Example 4 Brief Clinical Test (2)

200 ml of the vaginal cleansing composition (SG3) prepared in Example 3was administrated externally once a day for 5 days to 100 volunteersconsisting of 42 patients suffering from vaginosis, and 58 normal womenranging from 20 to 50 years who live in Korea. The difference of in thevaginal pH between the pH of (A) before and (B) after the treatment withthe composition was determined using a pH meter from Yuyuinst Co., Korea(MP-103).

TABLE 5 pH difference pH SAMPLE <3.5 4 4.5 5 5.5 6 >6.5 SUM A 0 2 7 9 1749 16 100 B 4 27 37 21 9 2 0 100

The results can be seen in Table 5. The vaginal pH of 82% of the testgroup before the treatment with the composition was more than 5.5;however, 89% of the test group after the treatment with the compositionreached a normal pH range.

Accordingly, it has been proved that the cleansing composition of SG3can be useful in decreasing the vaginal pH of the patients sufferingwith vaginal alkalization.

A composition comprising a combination of salt and sugar showed potentantibacterial activity, especially Gardnerella vaginalis, a main causeof vaginosis, as well as, stimulating the production of lactic acid tomaintain the vagina acidity by way of stimulating the proliferation ofLactobacillus acidophilus. Accordingly, the combination can be useful intreating or preventing vaginosis and useful in decreasing the vaginal pHof the patients suffering with vaginal alkalization.

The disclosure shows it is possible to vary the compositions in manyways. Such variations are not to be regarded as a departure from thespirit and scope of the present disclosure, and all such modificationsas would be known to one skilled in the art are intended to be includedwithin the scope of the following claims.

1. A composition comprising: a sea salt and a sugar; wherein the seasalt and sugar have a mixed weight ratio from 1:1 to 1:30, wherein theweight of the sugar is equal to or greater than the weight of any otheringredient in the composition and wherein the total weight of the sugarand the sea salt is from 80% to 100% of the total weight of thecomposition.
 2. (canceled)
 3. (canceled)
 4. The composition of claim 1,wherein the sea salt is sodium chloride.
 5. The composition of claim 1,wherein the sugar is glucose.
 6. The composition of claim 1, whereincomposition is a topical preparation selected from the group consistingof a cleansing liquid, gel, jelly, foam, cream, ointment, lotion, balm,patch, paste, spray solution, and aerosol.
 7. The composition of claim6, wherein the composition is a cleansing liquid.
 8. The composition ofclaim 1, wherein composition is an insert preparation selected from thegroup consisting of tablet, capsule, film, sponge, tampon and pad. 9.The composition of claim 8, wherein the composition is a tablet.
 10. Thecomposition of claim 1, further comprising dissolving the composition ina liquid at a percentage of the composition to the liquid from 0.01% to99.99%.
 11. The composition of claim 10, wherein the percentage of thecomposition to the liquid is from 5% to 10%.
 12. The composition ofclaim 10, wherein the liquid is selected from the group consisting ofdistilled water, a buffered solution, an isotonic solution, aphysiological saline, an oil, propylene glycol, ethanol and isopropylmyristate.
 13. A method of treatment comprising a) administering to amammal the composition of claim 1; and b) placing the composition in avagina of the mammal in need of treatment for a bacterial vaginosisinfection, wherein the bacterial vaginosis infection is a Gardnerellavaginalis infection.
 14. The method of claim 13, wherein the treatmentis selected from the group consisting of inhibition of development ofthe Gardnerella vaginalis infection, alleviation of the Gardnerellavaginalis infection and elimination of the Gardnerella vaginalisinfection.
 15. The method of claim 13, wherein administering to themammal comprises administering an amount of the composition in claim 1ranging from 0.001 mg to 1000 mg per kilogram of body weight of themammal.
 16. The method of claim 15, wherein the amount of thecomposition in claim 1 ranges from 0.01 mg to 100 mg per kilogram ofbody weight of the mammal.
 17. The method of claim 13, wherein thecomposition is administered from once a day to several times per day.